ABSTRACT This proposal requests support for a 5-year Keystone Symposia meeting series on the Cellular and Molecular Basis of Metabolic Disorders. The meetings for 2010 and beyond will build upon the best of Keystone Symposia's tradition in this area including cutting-edge research, dynamic critical discussions, interdisciplinary discovery and problem-solving, building networks and collaborations, and developing the next generation of investigators. Year 1 consists of six meetings. The Adipose Tissue Biology meeting considers the role of angiogenesis in adipose tissue expansion; the white fat-brown fat debate; the contribution of the circadian clock to hormonal and neural signals coordinating food intake and activity for metabolic balance; and the role of central and peripheral signals in the unanticipated lipodystrophic disorders resulting from such therapeutic regimens as antipsychotics and anti-retrovirals. The concurrent Neuronal Control of Appetite, Metabolism and Weight meeting addresses the crucial need for deeper understanding of the complex mechanisms of body weight homeostasis and dysfunctions leading to obesity and associated disorders. These joint meetings take advantage of critical interaction between the CNS and adipose tissue for control of energy homeostasis, and exploring dysfunction in this communication associated with the onset of obesity and diabetes. Nuclear Receptors: Signaling, Gene Regulation, and Cancer aims to understand how the ligand-dependent molecular actions of Nuclear Receptors (NRs) - including subcellular localization, binding across the genome, and interaction with the proteome - connect to their roles in physiological and pathophysiological processes, including hormone-regulated cancers. This meeting also examines NRs as targets for drug development. The concurrent Nuclear Receptors: Development, Physiology and Disease meeting focuses on the roles of NRs in development, physiology, and metabolism, and on their involvement in human disease. This emphasizes integration of molecular mechanisms of transcriptional control, normal development and physiology, disease initiation and progression, approaches to therapeutic intervention, and diseases that arise from NR dysfunction. Islet Biology critically discusses advances in several areas of islet research including development, regeneration, stem cells, transcription factors, novel signaling pathways, cell biology, genetics, gene regulation, drug targeting, and emerging technologies. This meeting explicitly addresses the ultimate goal of designing effective approaches to improve pancreatic ss-cell function and survival in Type 2 diabetes and generating ss-cells for transplantation in Type 1 diabetes. The concurrent Diabetes meeting explores Type 2 diabetes pathogenesis and possible therapeutics via research in many different fields, and capitalizes on genetic, genomic and physiological perspectives. The aim is to resolve the complex biology underpinning development of Type 2 diabetes and its associated metabolic disorders. The meeting also discusses new technical advances designed to penetrate the molecular pathogenesis of Type 2 diabetes.